Regulation of NF-κB by the CARD proteins

Changying Jiang1, Xin Lin

  • 1Department of Molecular and Cellular Oncology, The University of Texas, M D Anderson Cancer Center, Houston, TX 77030, USA.

Immunological Reviews
|March 23, 2012
PubMed

Insights

Scaffold proteins with caspase-recruitment domains (CARD) are crucial for activating nuclear factor-kappa B (NF-κB). This review details their roles in diverse signaling pathways, including those initiated by antigen receptors and G protein-coupled receptors.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Immunology

Background:

  • Scaffold proteins are key regulators of signal transduction, linking receptors to effectors.
  • Caspase-recruitment domain (CARD) containing scaffold proteins have emerged as critical players in cellular signaling.
  • Many CARD proteins are involved in activating nuclear factor-kappa B (NF-κB), a central transcription factor.

Purpose of the Study:

  • To review the contributions of CARD proteins to NF-κB activation across various signaling cascades.
  • To highlight the roles of the CARMA family of CARD proteins based on personal research experiences.
  • To summarize recent advancements in understanding CARD protein functions in response to diverse receptor types.

Main Methods:

  • Literature review and synthesis of existing research on CARD proteins and NF-κB.
  • Analysis of signaling pathways involving antigen receptors, G protein-coupled receptors, receptor tyrosine kinases, and C-type lectin receptors.
  • Inclusion of personal research findings on CARMA family proteins.

Main Results:

  • CARD proteins are integral to multiple signaling pathways that culminate in NF-κB activation.
  • The CARMA family of CARD proteins plays significant roles in immune and inflammatory responses.
  • Diverse receptor types, including GPCRs and RTKs, utilize CARD proteins to modulate NF-κB signaling.

Conclusions:

  • CARD proteins are essential mediators of NF-κB activation in response to a wide array of stimuli.
  • Understanding CARD protein function provides insights into immune regulation and inflammatory diseases.
  • Future research on CARD proteins will likely uncover further roles in cellular signaling and disease pathogenesis.

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...